P557: LIFETIME CLINICAL OUTCOMES OF CPX-351 VERSUS 7 + 3 MODELED FROM THE 5-YEAR RESULTS OF A RANDOMIZED PHASE 3 TRIAL FOR OLDER ADULTS WITH NEWLY DIAGNOSED HIGH-RISK OR SECONDARY ACUTE MYELOID LEUKAEMIA
Authors: Odette Reifsnider, Ben Yarnoff, Hila Shoval, Lin Fan
Journal: HemaSphere (2023)

Background: CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine at a synergistic 1:5 molar ratio, significantly prolonged median overall survival (OS; 9.56 vs 5.95 months; hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.52-0.90) and demonstrated a higher rate of complete remission (CR) or CR with incomplete neutrophil or platelet recovery (CRi) (47.7%) compared to standard 7 + 3 induction (33.3%) based on primary results from Study 301, the phase 3 trial (NCT01696084) of older patients (60-75 years) with newly-diagnosed high-risk or secondary acute myeloid leukaemia. Median OS was maintained even after 5 years of follow-up from Study 301 (Lancet Haematol. 2021;8(7):e481-e491). Further, more patients achieved haematopoietic stem cell transplantation (HSCT) with CPX-351 (34.0%) vs 7 + 3 (25.0%) and of those patients that did achieve HSCT (most of which were in CR/CRi), a significant OS benefit was observed for patients who received CPX-351 (HR, 0.51; 95% CI, 0.28-0.90). Aims: The 5-year trial data does not capture the full lifetime benefits in patients with newly-diagnosed high-risk or secondary acute myeloid leukaemia treated with CPX-351 vs 7 + 3. Therefore, we used a simulation model to estimate lifetime clinical benefits on the basis of the 5-year trial data. Methods: A hybrid decision tree-survival partition model, leveraging post hoc analyses of individual patient data from Study 301 (153 patients randomized to CPX:351 and 156 patients randomized to 7 + 3), simulated patients’ outcomes with CPX-351 vs 7 + 3 over a lifetime horizon. Patients were modeled in treatment pathways, defined by whether they achieved CR/CRi following induction and then underwent HSCT, based on observed trial data. Survival curves to estimate OS and event-free survival (EFS) over patients’ lifetimes were projected based on the treatment patients received and patients’ characteristics (age and AML subtype) using statistical extrapolation of 5-year trial follow-up data. This approach quantifies which pathways contribute to OS and captures the role of HSCT on OS. Subgroup analysis in patients who achieved CR/CRi and received HSCT was conducted. A range of scenarios with alternative model assumptions and inputs were tested through sensitivity and scenario analyses. Results: Results from the simulation model demonstrated that receiving CPX-351 compared to 7 + 3 increased life years (LYs) by 59% (3.07 vs 1.93 LYs, respectively) and doubled event free life years (EfLYs; 2.38 vs 1.19, respectively) (Table 1). These gains reflect longer survival among patients who achieved CR/CRi with CPX-351 compared to 7 + 3, and that a larger proportion of CPX-351 patients received HSCT. Among patients who achieved CR/CRi and received HSCT, treatment with CPX-351 was estimated to provide 9.66 LYs and 8.85 EfLYs compared to 5.57 LYs and 5.19 EfLYs with 7 + 3, a 73% increase in LYs and 70% increase in EfLYs. The results remained robust in sensitivity analyses. Summary/Conclusion: Extrapolation of 5-year follow-up data from the CPX-351 pivotal clinical trial using a simulation model suggests a substantial lifetime survival benefit from CPX-351 vs 7 + 3 in patients with newly-diagnosed high-risk or secondary acute myeloid leukaemia, particularly for patients who both achieved CR/CRi and received HSCT.Keywords: Stem cell transplant, Acute myeloid leukemia, Survival